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MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells
The neurotransmitter acetylcholine (ACh) promotes the growth and metastasis of several cancers via its M3 muscarinic receptor (M3R). Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is overexpressed in gastric cancer (GC) and plays an important role in GC progression, though it is...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951273/ https://www.ncbi.nlm.nih.gov/pubmed/26919111 http://dx.doi.org/10.18632/oncotarget.7634 |
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author | Yang, Ting He, Wanming Cui, Fei Xia, Jianling Zhou, Rui Wu, Zhenzhen Zhao, Yang Shi, Min |
author_facet | Yang, Ting He, Wanming Cui, Fei Xia, Jianling Zhou, Rui Wu, Zhenzhen Zhao, Yang Shi, Min |
author_sort | Yang, Ting |
collection | PubMed |
description | The neurotransmitter acetylcholine (ACh) promotes the growth and metastasis of several cancers via its M3 muscarinic receptor (M3R). Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is overexpressed in gastric cancer (GC) and plays an important role in GC progression, though it is unclear how MACC1 activity is regulated in GC. In this study, we demonstrated that ACh acts via M3Rs to promote GC cell invasion and migration as well as expression of several markers of epithelial-mesenchymal transition (EMT). The M3R antagonist darifenacin inhibited GC cell activity in both the presence and absence of exogenous ACh, suggesting GC cells secrete endogenous ACh, which then acts in an autocrine fashion to promote GC cell migration/invasion. ACh up-regulated MACC1 in GC cells, and MACC1 knockdown using siRNA attenuated the effects of ACh on GC cells. AMP-activated protein kinase (AMPK) served as an intermediate signal between ACh and MACC1. These findings suggest that ACh acts via a M3R/AMPK/MACC1 signaling pathway to promote GC cell invasion/migration, which provides insight into the mechanisms underlying GC growth and metastasis and may shed light on new targets for GC treatment. |
format | Online Article Text |
id | pubmed-4951273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49512732016-07-21 MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells Yang, Ting He, Wanming Cui, Fei Xia, Jianling Zhou, Rui Wu, Zhenzhen Zhao, Yang Shi, Min Oncotarget Research Paper The neurotransmitter acetylcholine (ACh) promotes the growth and metastasis of several cancers via its M3 muscarinic receptor (M3R). Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is overexpressed in gastric cancer (GC) and plays an important role in GC progression, though it is unclear how MACC1 activity is regulated in GC. In this study, we demonstrated that ACh acts via M3Rs to promote GC cell invasion and migration as well as expression of several markers of epithelial-mesenchymal transition (EMT). The M3R antagonist darifenacin inhibited GC cell activity in both the presence and absence of exogenous ACh, suggesting GC cells secrete endogenous ACh, which then acts in an autocrine fashion to promote GC cell migration/invasion. ACh up-regulated MACC1 in GC cells, and MACC1 knockdown using siRNA attenuated the effects of ACh on GC cells. AMP-activated protein kinase (AMPK) served as an intermediate signal between ACh and MACC1. These findings suggest that ACh acts via a M3R/AMPK/MACC1 signaling pathway to promote GC cell invasion/migration, which provides insight into the mechanisms underlying GC growth and metastasis and may shed light on new targets for GC treatment. Impact Journals LLC 2016-02-23 /pmc/articles/PMC4951273/ /pubmed/26919111 http://dx.doi.org/10.18632/oncotarget.7634 Text en Copyright: © 2016 Yang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Yang, Ting He, Wanming Cui, Fei Xia, Jianling Zhou, Rui Wu, Zhenzhen Zhao, Yang Shi, Min MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells |
title | MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells |
title_full | MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells |
title_fullStr | MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells |
title_full_unstemmed | MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells |
title_short | MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells |
title_sort | macc1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951273/ https://www.ncbi.nlm.nih.gov/pubmed/26919111 http://dx.doi.org/10.18632/oncotarget.7634 |
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